Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis

NCT03768089 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: VX17-121-0012018-000126-55
• Study Type: interventional
• Target: 115
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to evaluate safety and tolerability of VX-121 in healthy subjects and in subjects with cystic fibrosis (CF).

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  From Day 1 Through Safety Follow-up (up to Day 15 for Part A [except Cohorts A3 and A9], up to Day 26 for Cohort A3, up to Day 34 for Cohort A9, up to Day 20 for Part B, up to Day 24 for Part C and up to Week 9 for Part D)

Secondary Outcomes (13)

• Part A: Maximum Observed Concentration (Cmax) of VX-121

  Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose

• Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121

  Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose

• Part B: Maximum Observed Concentration (Cmax) of VX-121

  Day 1, Day 5, and Day 10

• Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121

  Day 1, Day 5, and Day 10

• Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121

  Pre-dose at Day 5 and Day 10

Study Arms (18)

Part A: Pooled Placebo (Cohorts A1-5; Except A3)

PLACEBO COMPARATOR

Participants received single dose of placebo matched to VX-121.

Drug: Placebo (matched to VX-121 suspension)

Part A: VX-121 (Cohort A1)

EXPERIMENTAL

Participants received single dose of VX-121 10 milligrams (mg).

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A2)

EXPERIMENTAL

Participants received single dose of VX-121 20 mg.

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A3)

EXPERIMENTAL

Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.

Drug: Placebo (matched to VX-121 suspension); Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A4)

EXPERIMENTAL

Participants received single dose of VX-121 40 mg.

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A5)

EXPERIMENTAL

Participants received single dose of VX-121 60 mg.

Drug: VX-121 (Suspension)

Part A: VX-121 (Cohort A9)

EXPERIMENTAL

Participants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17.

Drug: VX-121 (Suspension); Drug: VX-121 (Tablet)

Part B: Pooled Placebo (Cohorts B1-4)

PLACEBO COMPARATOR

Participants received placebo matched to VX-121 for 10 days.

Drug: Placebo (matched to VX-121 suspension)

Part B: VX-121 (Cohort B1)

EXPERIMENTAL

Participants received VX-121 10 mg once daily (qd) for 10 days.

Drug: VX-121 (Suspension)

Part B: VX-121 (Cohort B2)

EXPERIMENTAL

Participants received VX-121 20 mg qd for 10 days.

Drug: VX-121 (Suspension)

Part B: VX-121 (Cohort B3)

EXPERIMENTAL

Participants received VX-121 40 mg qd for 10 days.

Drug: VX-121 (Suspension)

Part B: VX-121 (Cohort B4)

EXPERIMENTAL

Participants received VX-121 60 mg qd for 10 days.

Drug: VX-121 (Suspension)

Part C: Pooled Placebo (Cohorts C1-3)

PLACEBO COMPARATOR

Participants received placebo matched to VX-121/TEZ/IVA for 14 days.

Drug: Placebo (matched to VX-121 suspension); Drug: Placebo (matched to TEZ/IVA); Drug: Placebo (matched to IVA)

Part C: VX-121 (Cohort C1)

EXPERIMENTAL

Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.

Drug: VX-121 (Suspension); Drug: TEZ/IVA; Drug: IVA

Part C: VX-121 (Cohort C2)

EXPERIMENTAL

Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

Drug: VX-121 (Suspension); Drug: TEZ/IVA; Drug: IVA

Part C: VX-121 (Cohort C3)

EXPERIMENTAL

Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

Drug: VX-121 (Suspension); Drug: TEZ/IVA; Drug: IVA

Part D: Placebo

PLACEBO COMPARATOR

Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.

Drug: Placebo (matched to TEZ/IVA); Drug: Placebo (matched to IVA); Drug: Placebo (matched to VX-121 tablet)

Part D: VX-121/TEZ/IVA

EXPERIMENTAL

Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.

Drug: TEZ/IVA; Drug: IVA; Drug: VX-121 (Tablet)

Interventions

Placebo (matched to VX-121 suspension) DRUG

Placebo matched to VX-121 suspension for oral administration.

Part A: Pooled Placebo (Cohorts A1-5; Except A3); Part A: VX-121 (Cohort A3); Part B: Pooled Placebo (Cohorts B1-4); Part C: Pooled Placebo (Cohorts C1-3)

VX-121 (Suspension) DRUG

Suspension for oral administration.

Part A: VX-121 (Cohort A1); Part A: VX-121 (Cohort A2); Part A: VX-121 (Cohort A3); Part A: VX-121 (Cohort A4); Part A: VX-121 (Cohort A5); Part A: VX-121 (Cohort A9); Part B: VX-121 (Cohort B1); Part B: VX-121 (Cohort B2); Part B: VX-121 (Cohort B3); Part B: VX-121 (Cohort B4); Part C: VX-121 (Cohort C1); Part C: VX-121 (Cohort C2); Part C: VX-121 (Cohort C3)

TEZ/IVA DRUG

Fixed-dose combination tablet for oral administration.

Also known as: VX-661/VX-770, tezacaftor/ivacaftor

Part C: VX-121 (Cohort C1); Part C: VX-121 (Cohort C2); Part C: VX-121 (Cohort C3); Part D: VX-121/TEZ/IVA

IVA DRUG

Tablet for oral administration.

Also known as: VX-770, ivacaftor

Part C: VX-121 (Cohort C1); Part C: VX-121 (Cohort C2); Part C: VX-121 (Cohort C3); Part D: VX-121/TEZ/IVA

Placebo (matched to TEZ/IVA) DRUG

Placebo matched to TEZ/IVA for oral administration.

Part C: Pooled Placebo (Cohorts C1-3); Part D: Placebo

Placebo (matched to IVA) DRUG

Placebo matched to IVA for oral administration.

Part C: Pooled Placebo (Cohorts C1-3); Part D: Placebo

VX-121 (Tablet) DRUG

Tablet for oral administration.

Part A: VX-121 (Cohort A9); Part D: VX-121/TEZ/IVA

Placebo (matched to VX-121 tablet) DRUG

Placebo matched to VX-121 tablet for oral administration.

Part D: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A, B, and C: Healthy Volunteers
• Female subjects must be of non-childbearing potential
• Between the ages of 18 and 55 years, inclusive
• Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight \>50 kg
• Part D: Subjects with CF
• Heterozygous for F508del and an MF mutation (F/MF)
• FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height
• Body weight ≥35 kg

You may not qualify if:

• Part A, B and C: Healthy Volunteers
• Any condition possibly affecting drug absorption
• History of febrile illness or other acute illness within 5 days before the first study drug dose
• Part D: Subjects with CF
• History of clinically significant cirrhosis with or without portal hypertension
• History of solid organ or hematological transplantation
• Lung infection with organisms associated with a more rapid decline in pulmonary status

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (7)

Academic Medical Center

Amsterdam, Netherlands

Location

PRA Health Sciences Onderzoekscentrum UMCG

Groningen, Netherlands

Location

UMC St. Radboud

Nijmegen, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

HagaZiekenhuis van den Haag

The Hague, Netherlands

Location

Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

The Medicines Evaluation Unit

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Suspensions; tezacaftor, ivacaftor drug combination; ivacaftor; Tablets

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 7, 2018
• Study Start: March 20, 2018
• Primary Completion: May 3, 2019
• Study Completion: May 3, 2019
• Last Updated: July 14, 2022
• Results First Posted: July 14, 2022

Record last verified: 2022-06

Locations

NL (5); GB (2)